Process analysis Raman spectrometry

In polymer/additive deformulation (of extracts, solutions and in-polymer), spectroscopic methods (nowadays mainly UV, IR and to a lesser extent NMR followed at a large distance by Raman) play an important role, and even more so in process analysis, where the time-consuming chromatographic techniques are less favoured. Some methods, as NMR and Raman spectrometry, were once relatively insensitive, but seem poised to become better performing. Quantitative polymer/additive analysis may benefit from more extensive use of 600-800 MHz 1-NMR equipped with a high-temperature accessory (soluble additives only). 

One indication of the developing interest in PATs in the pharmaceutical area is the number of book chapters and review articles in this field that have appeared in the last few years. Several chapters in The Handbook of Vibrational Spectroscopy3 are related to the use of various optical spectroscopies in pharmaceutical development and manufacturing. Warman and Hammond also cover spectroscopic techniques extensively in their chapter titled Process Analysis in the Pharmaceutical Industry in the text Pharmaceutical Analysis.4 Pharmaceutical applications are included in an exhaustive review of near-infrared (NIR) and mid-infrared (mid-IR) by Workman,5 as well as the periodic applications reviews of Process Analytical Chemistry and Pharmaceutical Science in the journal Analytical Chemistry. The Encyclopedia of Pharmaceutical Technology has several chapters on spectroscopic methods of analysis, with the chapters on Diffuse Reflectance and Near-Infrared Spectrometry particularly highlighting on-line applications. There are an ever-expanding number of recent reviews on pharmaceutical applications, and a few examples are cited for Raman,7 8 NIR,9-11 and mid-IR.12... 

Infrared spectrometry is currently exploited in process analysis but less so than near IR and Raman spectrometry. The reasons for this are the strong absorbances of most mid IR bands and the sensitivity of mid IR optical materials to chemical erosion. There is also a relative lack of practical hbre optic options for use in the mid IR range since silver halide and chalcogenide glasses, which cover the whole of the mid IR region, can attenuate the radiation by as much as 95%, even over short distances. Other hbres such as zirconium fluoride cut off below 2500 cm and so the fingerprint region information is lost. 

Ultraviolet (UV)-visible spectrometry, near-infrared spectrometry, mid-infrared spectrometry, and Raman spectrometry have all been used for online process analysis (including inline and noninvasive applications). 

Methods for competitive analysis, troubleshooting process and product problems, plastics analysis, analysis of failed products and analysis of polymeric formulations are discussed. Procedures covered include FTIR spectroscopy, Raman spectroscopy, NMR spectroscopy, surface analysis by spectroscopy, gas chromatography/mass spectrometry, atomic force microscopy and techniques for analysing unidentified formulations. 47 refs. 

---